Prior to the present invention, most methods for determining specific gravity utilized hydrometers, urinometers, pycnometers, gravimeters and the like. Although these prior art procedures are satisfactorily sensitive in most cases, they involve fragile, bulky instruments which must be constantly cleaned, maintained, and calibrated in order to continuously assure their reliability. In addition, there are many inconveniences associated with the mechanics of using these instruments. There may be a difficulty in reading the miniscus. Froth or bubbles on the liquid surface may interfere with the reading. There is a tendency for urinometers to adhere to the sides of the vessel containing the liquid sample. In the case of urine, the sample quantity is frequently inadequate for accommodating one of the aforementioned devices.
A recent breakthrough in which all of the above disadvantages have been virtually eliminated, and which affords rapid osmolality (ergo, specific gravity) determination, is disclosed in U.S. Pat. No. 4,015,462, issued to Greyson, et al., and assigned to the present assignee. This patent describes an invention in which a carrier matrix is incorporated with osmotically fragile microcapsules, the walls of which are composed of a semi-permeable membrane material. Encapsulated inside the walls is a solution containing a coloring substance. When the capsules come in contact with a solution having a lower osmolality than that within the capsules, an osmotic gradient occurs across the capsule walls in the direction of the lower osmolality, thereby increasing the hydrostatic pressure within the capsules, thus causing them to swell and, ultimately, to rupture, releasing their colored contents. The amount of color formed from this phenomenon is a function of the specific gravity of the solution.
Thus, it is seen that, besides the numerous devices which measure specific gravity directly, it is also possible to measure specific gravity using an indirect means such as the osmolality of a solution.
Yet another way of estimating specific gravity without measuring it directly involves a determination which is proportional to the ionic strength of a solution, the correlation of which parameters has already been discussed in section 1.1, supra. Such an approach is utilized in U.S. Pat. No. 4,318,709 issued to Falb, et al., and assigned to the present assignee. Since it is well known that the specific gravity of an aqueous system is greatly affected by the presence of charged species, it is possible to closely approximate the specific gravity of the respective solutions via measurements proportional to their ionic strengths, and refer those measurements to a precalibrated reference system. The Falb, et al., patent makes use of such a relationship.
The Falb et al. patent discloses the use of weakly acidic or basic polyelectrolytes which have been at least 50% neutralyzed with a base (such as NaOH) or an acid (such as HCl), respectively. Depending on the ionic strength of the test solution, an intramolecular pH change may occur in the polymer, the degree of which is a barometer of ionic strength. A pH indicator such as a pH meter or pH-sensitive compound reflects the pH change (or lack thereof) instigated by the sample ionic strength.
Both the osmolality approach and the ionic strength approach to indirectly determining specific gravity could conceivably be affected insofar as accuracy is concerned by the presence of nonionic species. However, it has been found that such nonionic constituents as glucose, protein and urea do not effectively lead to anomalous or substantially inaccurate results with the Falb, et al. test except at very high concentrations. See Burkhardt, et. al., Clinical Chemistry, 28, 2068-2072 (1982).
U.S. Pat. No. 4,108,727 is directed to a method for removing this potential source of inaccuracy, and discloses a device in which the specific gravity-sensitive system contains an ionizing agent capable of converting the nonionic solute to ionized species.
U.S. Pat. No. 3,449,080 discusses measuring dissolved sodium or chloride ions. This reference is directed to a test device for determining the concentrations of these ions in body sweat. There is disclosed in this patent the use of ion exchange resins together with a pH indicator. Using this device, the presence of sodium or chloride ions is said to be determined through a color change in the ion exchange resin caused by the pH indicator. Whereas this reference purports to disclose a way of measuring ionic strength, it was found by the present inventors that such teachings, as set forth in the examples, were inapplicable to the measurement of specific gravity.
To summarize the present background of specific gravity measurement prior to the present invention, many methods are known for assaying that solution parameter, both direct and indirect. Direct measurement includes utilizing devices which are fragile, bulky and expensive, and which must be constantly cleaned, maintained and calibrated. Of the indirect methods, the measurement of the colligative solution property known as osmolality can provide an accurate correlation to specific gravity. In addition, the relationship between specific gravity and the ionic strength of a solution can be employed, by utilizing partially neutralized polyelectrolytes and a pH indicator. Weak polyelectrolytes are said to be useful in gauging the concentration of sodium and/or chloride ions in body sweat.
The present invention provides a departure from the prior art which enables dramatic improvements in the measurement of ionic strength, ergo specific gravity. Practice of the invention affords greater sensitivity in differentiating various specific gravity levels, as well as enhanced resistance to interference from test sample-to-test sample pH variations.